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pmid:28042536
Central Nodes in Protein Interaction Networks Drive Critical Functions in Transforming Growth Factor Beta-1 Stimulated Kidney Cells.
Reyhaneh Rabieian · Maryam Abedi · Yousof Gheisari
Cell journal · 2017 doi:10.22074/cellj.2016.4718
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Complete file
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Many studies have shown a central role for transforming growth factor beta-1 (TGFβ-1) and its downstream signaling cascades in the pathogenesis of CKD. In this study, we have reanalyzed a microarray dataset to recognize critical signaling pathways controlled by TGFβ-1.\nMATERIALS AND METHODS: This study is a bioinformatics reanalysis for a microarray data. The GSE23338 dataset was downloaded from the gene expression omnibus (GEO) database which assesses the mRNA expression profile of TGFβ-1 treated human kidney cells after 24 and 48 hours incubation. The protein interaction networks for differentially expressed (DE) genes in both time points were constructed and enriched. In addition, by network topology analysis, genes with high centrality were identified and then pathway enrichment analysis was performed with either the total network genes or with the central nodes.\nRESULTS: We found 110 and 170 genes differentially expressed in the time points 24 and 48 hours, respectively. As the genes in each time point had few interactions, the networks were enriched by adding previously known genes interacting with the differentially expressed ones. In terms of degree, betweenness, and closeness centrality parameters 62 and 60 nodes were considered to be central in the enriched networks of 24 hours and 48 hours treatment, respectively. Pathway enrichment analysis with the central nodes was more informative than those with all network nodes or even initial DE genes, revealing key signaling pathways.\nCONCLUSION: We here introduced a method for the analysis of microarray data that integrates the expression pattern of genes with their topological properties in protein interaction networks. This holistic novel approach allows extracting knowledge from raw bulk omics data.", "claims": [{"id": "claim-method", "statement": "Benjamini-Hochberg false discovery rate method was applied for P value adjustment.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28042536", "locator": "sections[3] \"Microarray data\" paragraph 2", "quote": "Benjamini-Hochberg false discovery rate method was applied for P value adjustment."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE23338 dataset was downloaded from the gene expression omnibus (GEO) database which assesses the mRNA expression profile of TGFβ-1 treated human kidney cells after 24 and 48 hours incubation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:28042536", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The GSE23338 dataset was downloaded from the gene expression omnibus (GEO) database which assesses the mRNA expression profile of TGFβ-1 treated human kidney cells after 24 and 48 hours incubation."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study used GEO2R with Benjamini-Hochberg false discovery rate adjustment to reanalyze the GSE23338 microarray dataset obtained from the Gene Expression Omnibus (GEO) database.", "kind": "quantitative", "target": {"value": 48.0, "unit": "odds ratio", "tolerance": null, "source": "Using GEO2R tool of GEO, the TGFβ-1 treated cells (24 or 48 hours) were compared to untreated HK-2 cells. 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Benjamini-Hochberg false discovery rate method was applied for P value adjustment."}, {"asset": "source:pmid:28042536", "locator": "sections[6] \"Results\" paragraph 2", "quote": "Analysis by GEO2R revealed that 110 genes after 24 hours and 170 genes after 48 hours were differentially expressed with adjusted P≤0.05 (Table 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study used GEO2R with Benjamini-Hochberg false discovery rate adjustment to reanalyze the GSE23338 microarray dataset obtained from the Gene Expression Omnibus (GEO) database.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:28042536"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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time 48 hours", "structure": {"pmcid": "PMC5086330", "section_index": 6, "section_title": "Results", "row_count": 49, "column_count": 6}, "table": {"label": "Table 3", "caption": "The top 15% genes with the best rank in degree, betweenness centrality, and closeness centrality parameters in the enriched proteinprotein interaction (PPI) network of time 48 hours", "rows": [[""], ["Genes", "Degree", "Genes", "Betweenness", "Genes", "Closeness"], [""], ["TP53", "55", "TP53", "0.218425", "JUN", "0.419966"], ["AKT1", "49", "AKT1", "0.180618", "TP53", "0.419244"], ["EGFR", "33", "EGFR", "0.129406", "AKT1", "0.415673"], ["SMAD3", "32", "JUN", "0.121849", "EGFR", "0.403974"], ["JUN", "32", "SMAD3", "0.091028", "AR", "0.403306"], ["AR", "28", "ALB", "0.08664", "SMAD3", "0.394184"], ["FN1", "25", "CTNNB1", "0.077284", "CTNNB1", "0.3904"], ["THBS1", "24", "AR", "0.063727", "SMAD4", "0.387917"], ["CTNNB1", "23", "SMAD4", "0.059499", "SERPINE1", "0.387917"], ["SMAD2", "23", "FN1", "0.056896", 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"SHH", "0.343662"], ["MAP3K5", "10", "CDKN2A", "0.022895", "SPOCK1", "0.343662"], ["ACVR2A", "10", "CD9", "0.021863", "GRB10", "0.343179"], ["ID2", "9", "NCOR1", "0.021568", "NOV", "0.342216"], ["MMP13", "9", "MAP3K5", "0.020279", "GSTA1", "0.33936"], ["SKIL", "9", "HNF1B", "0.020242", "TCF4", "0.338889"], ["SPOCK1", "9", "SPOCK1", "0.018718", "FAS", "0.336088"], ["PDLIM7", "9", "CTBP1", "0.018114", "CDKN2A", "0.335626"], ["KDR", "9", "TPM1", "0.018056", "NCOR1", "0.335626"], ["LRP2", "9", "PTHLH", "0.017657", "TGFBI", "0.335165"], ["TCF3", "9", "TBL1X", "0.016927", "VCAN", "0.334705"], ["NOV", "8", "CSF2", "0.015788", "HSPA5", "0.334247"], ["PTHLH", "8", "GSTA1", "0.015304", "CLTCL1", "0.333333"], ["CDKN1B", "8", "KDR", "0.015185", "SKIL", "0.333333"], ["GADD45A", "8", "MMP13", "0.014604", "PLG", "0.332879"], ["GRB10", "8", "ANXA2", "0.01411", "PTHLH", "0.332879"], ["LAMA5", "8", "CLTCL1", "0.013602", "PRKAR2A", "0.332425"], ["VTN", "8", "MAPK1", "0.012772", "MAP3K5", "0.330623"], 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